Despite the widespread practice of basic and advanced life support, over 1000 patients die each day in the United States from an out-of-hospital cardiac arrest. Even though they receive standard cardiopulmonary resuscitation (sCPR) the average national survival to hospital discharge for these patients is less than 5%. The applicants have developed the inspiratory impedance threshold device (ITD) to increase negative intrathoracic pressure during the decompression phase of sCPR, thereby doubling forward blood flow. The Phase 2 clinical trial demonstrated that intensive care unit admission rate (primary study endpoint) in patients with an initial heart rhythm of pulseless electrical activity increased from 19% to 52% (p=0.02). During Phase 2 investigators also discovered a fundamental new principle of blood flow during CPR: an inverse relationship between intrathoracic pressure and coronary perfusion pressure as well as cerebral perfusion pressure and survival rates. With increased intrathoracic pressure, coronary and cerebral perfusion pressures, as well as survival rates, decreased. The Phase 2 research further lead to the discovery that during sCPR ventilation rates and duration are often excessive and that the chest is often not allowed to fully recoil after each compression. Each of these common clinical errors was electronically recorded for the first time and then shown to be detrimental, if not deadly, in animal models of cardiac arrest. Based upon these Phase II results the applicants have improved the ITD by adding a ventilation timing light to guide proper ventilation and developed a new and improved hand position for sCPR to help promote full chest wall recoil. Another way to assure that the critically important full chest recoil occurs after each chest compression is by using active compression decompression (ACD) CPR, a technique also developed by the applicants that utilizes a hand held device. Based upon these Phase 2 results, the Phase 2 continuation research will be conducted to obtain sufficient clinical data for regulatory clearance for the ITD as a technology intended to improve 24-hour survival rates after cardiac arrest. A pivotal clinical trial is proposed in the form of a prospective, randomized, two-site clinical trial to: 1) determine the 24-hour survival rate when using the ITD with improved sCPR, and 2) to determine the 24-hour survival rate when using the ITD and assuring full chest wall recoil with ACD CPR. With 400,000 out-of-hospital deaths from cardiac arrest in the United States alone, widespread application of this technology could result in 50,000 additional survivors per year.